Motor Fatigue in Multiple Sclerosis: Role of Central Mechanisms
Abstract
Rationale, Objectives and Research Strategy: Fatigue is a complex phenomenon, particularly common and disabling in people with multiple sclerosis (PwMS). Approximately 70% to 90% of PwMS experience difficulties in initiating and/or sustaining physical activities (motor fatigue) during daily life. Importantly, motor fatigue can worsen other symptoms associated with disease, e.g., balance control and mobility impairments, thereby worsening the quality of life in PwMS. Despite the high prevalence of motor fatigue, there is no specific treatment for this debilitating symptom. One critical barrier to the road of effective interventions for fatigue in MS is the lack of clear understanding of the underlying mechanisms. The main objective of the proposed study is to determine the role of central factors in motor fatigue in MS and to investigate the alterations in the brain connectivity patterns underlying central fatigue. In addition, we will examine the acute effects of motor fatigue on balance control during standing (standing balance) and walking (dynamic balance) in PwMS. Thirty (30) PwMS and 30 healthy controls in the age group 18-65 years will participate in a motor task that will require them to push against the footplate of a force dynamometer as hard as possible for 60 seconds. The decline in the maximum force output of the plantar-flexor muscles over 60 seconds will be defined as motor fatigue and the decline in the voluntary activation, as determined by the twitch interpolation technique, will be defined as central fatigue. Additionally, resting-state functional magnetic resonance imaging will be implemented to investigate the connectivity between the cortico-striatal connections. Specifically, the severity of central fatigue will be associated with the functional connectivity of the motor circuit of the basal ganglia. A positive association between central fatigue and increased functional connectivity will represent a compensatory mechanism to overcome the consequences of neurological damage on motor function in PwMS, but at the expense of increased exhaustion during the course of motor activity. Finally, innovative body-worn wireless inertial sensors will be used to determine standing balance pre-and post-fatigue test, and the dynamic balance will be tested during a fast 6-minute walk test. Changes in both standing and the dynamic balance will be compared to central fatigue. Focus Area: Our proposed project falls under the “Biology, Measurement, or Treatment of MS Symptoms Focus area” in the category of “MS symptoms: Fatigue” and subcategories of “mechanisms underlying symptoms of MS,” and “development and/or validation of outcome measures and tools for symptoms.” The project investigators have extensive backgrounds in MS, rehabilitation, objective assessment of motor function and fatigue, as well as neuroimaging. Our project takes advantage of all of our areas of expertise and therefore offers a multidisciplinary approach to explore central mechanisms underlying motor fatigue in MS. Applicability of the Research to MS Patient Care: This research will help people with neurological MS (including those with MS), in whom fatigue hampers the performance of activities of daily living. Though common, motor fatigue is often under-emphasized in clinics. For example, about 70% to 90% of U.S. Veterans with MS report moderate to high fatigue levels, but only 40% are treated for fatigue. This is of particular concern, given the effect that motor fatigue has on patients and families, and the unavailability of effective medications with longer-term effects. Our study will establish the feasibility of using an objective physiological biomarker for fatigue quantification and an imaging biomarker for unmasking the underlying mechanisms of central fatigue. If the objective biomarkers of central fatigue are developed and a clear understanding of the underlying neural alterations is established, it will facilitate the prevention
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810425
Entities
People
- Fay B Horak
Organizations
- Oregon Health & Science University
- United States Army